Single Voxel MR Spectroscopy in Non-Herniated Painful, Herniated Painful, and Non-Painful Lumbar Discs

Transcription

1 Single Voxel MR Spectroscopy in Non-Herniated Painful, Herniated Painful, and Non-Painful Lumbar Discs PG Lactate col L Tanenbaum 1, S Hu 2, M Gornet 3, S Berven 2, J Peacock 4, J Lotz 2,4, D Bradford 4, J Claude 4, P Kane 4, F Schranck 3, D Stewart 5 1 Icahn School of Medicine at Mount Sinai, 2 University of California San Francisco, 3 Orthopedic Center of Saint Louis, 4 Nocimed, LLC, 5 MRI Partners of Chesterfield 1

2 Disclosures Tanenbaum, L: Nocimed, LLC - advisory board Bradford, D; Lotz, J: Nocimed, LLC - management, shareholder, royalty Kane, P; Claude, J: Nocimed, LLC - shareholder, consulting Peacock, J: Nocimed, LLC - management, shareholder Schranck, F; Gornet, M: The Orthopedic Center of St. Louis - Nocimed sponsored research grant, Nocimed, LLC - shareholder 2

3 Purpose Evaluate non-invasive in vivo single voxel MR spectroscopy (SVS) in lumbar discs on two commercial 3T scanners - GE Signa & Siemens Verio for a) discogenic low back pain (LBP) pain patients receiving provocative discography (PD), and b) asymptomatic control volunteers (ASY) Correlate results to clinical phenotypes non-herniated painful (NHP) herniated painful (HP) non-painful (NP) discs 3

4 Background Disc degeneration altered disc structure and biochemical composition that may or may not cause pain decreased proteoglycan synthesis increase matrix catabolism features that differentiate painful from non painful degenerative discs not well understood. *Buser, 2010 Spine: Affiliated Society Meeting Abstracts

5 Background Disc degeneration consistent changes in markers of hypoxia, innervation and inflammation showed strong correlation with discs associated with pain Nucleus samples Gene expression with highest correlation between painful vs. nonpainful discs relate to (R2=.67): 1. hypoxia - lactate dehydrogenase; 2. innervation - nerve growth factor. *Buser, 2010 Spine: Affiliated Society Meeting Abstracts

6 Background Identifying the painful disc Painful discs are distinguished by hypoxia, inflammation, neovascularization & neoinnervation* Consistent changes in biomarkers/chemical mediators detectable and quantifiable with MR spectroscopy *Freemont, A. J., (2009) Rheumatology; 48:5 10.

7 Non-Painful Disc (Scoliosis) n=9 Background-Ex vivo Disc SVS, 11T HR MAS Surgical Samples PG/LA PG Lactate p<.005 col Painful Disc (PD+, LBP) n=9 Lactate col PG Keshari, Spine (3): p

8 Materials & Methods Iterative technical development protocol Conducted in series: GE ( ), Siemens ( ) T1/T2 weighted imaging sequences SVS acquisition, each lumbar disc sequentially Inter-platform differences: OVS bands: GE only (not used for Siemens) Autoshim Auto + Manual shim: Siemens protocol refinement Manual voxel localization in disc to remove end-plates 9

9 Materials & Methods Acquisition Systems GE Signa HDxt 3.0T, v14x HDCTL 456 spine coil Pulse Sequence: custom Chess/Press modified PROSE TM for disc SVS: TR=1500, TE=28ms Siemens 3T Verio, Model Numaris/4 Spine Coil Model Pulse Sequence: SVS Syngo VB17 Version 1.0 investigational patch for 3-5mm voxel height Both single center, Nocimed sponsored, IRB approved GE 3T: University of California at San Francisco Siemens 3T: The Orthopedic Center of St. Louis 10

10 Materials & Methods signal post-processing Non-Painful Disc Non- Painful Automated Channel Select Frame Edit Phase/Freq Apodize Aggregate Baseline 11

11 Materials & Methods technical success & signal quality assessment GE data: initial in vivo development cycle of entire approach Reported data not include technical failures for poor signal quality Technical failures = only indeterminate results of Dx correlation algorithm SIEMENS data: x-platform application/refinement of prior learning Less technical development required Reported data includes all completed acquisitions - signal quality successes & failures Primary Signal (satisfactory) Quality Assessment Criteria: o SNR > 3 for PG or LA peak regions o Water FWHM < 35 Hz o Presence (fail) or Absence (accept) of lipid motion artifact 12

12 Materials & Methods diagnostic interpretation/correlation to disc type Different approach per platform, serial development phases Earlier GE platform data: Multi-variate (PG & LA) automated statistical algorithm development via JMP logistic regression software Predictive value of SVS biomarker measures for painful vs. non-painful Later Siemens platform data: Simple PG/LA ratio Predictive value/statistical modeling planned (> more pain patients) 1% 1% 99% 13

13 Materials & Methods study design inclusion criteria Male and non-pregnant females, yrs old Pain group: Oswestry Disability Index 40%, or Visual Analog Scale 4 Indicated for Lumbar Spine Provocation Discography (PD) Practice Guidelines for Spinal Diagnostic and Treatment Procedures (ISIS, 2004) PD performed 6wk-6mo before, or 1mo after, Disc SVS exam Up to 12 mo before in earlier GE study Asymptomatic control volunteers: Absent chronic severe LBP VAS 1, ODI

14 Materials & Methods study design exclusion criteria Complicating extradiscal pain sources fracture, spondylolisthesis, spondylolysis Prior lumbar surgery or intradiscal treatments except diagnostic provocative or anesthetic discography Chronic disease or pain, or psychological dysfunction, relevant to study objectives 15

15 GE study n= 42 Subjects, 79 Discs 1 Pain Pts (PD) n=14 Volunteers n=28 Painful Discs (PD+) Non-Painful Discs (PD-) Non-Painful Discs (assumed) n = 15 n = 49 n = 15 + Control, Painful n = 64 - Control, Non-Painful 16

16 Siemens study n=33 Subjects, 130 Discs 1 Pain Pts (PD) n=14 Volunteers n=19 Non-Herniated Painful Discs (PD+) Herniated Painful Discs (PD+) Non-Painful Discs (PD- & remote levels) Non-Painful Discs (assumed) n = 16 n = n = 3 2 n = 9 n = Includes n=1 disc excluded from analysis as non-lumbar (S1-S2) 2 Includes n=1 disc analyzed separately due to extra discal co-morbidities (spondylosis + facet arthropathy) 17

17 Results- 3T GE Signa Case 1, Pain Pt (PD+ L5S1, PD- L4L5) Discogram: +/- - + Hu, Orthopaedic Research Society

18 Results - GE 3T Signa 94% (74/79) Determinate, 99% (73/74) Accurate (PG,LA) PG & LA-related Dx Algorithm score SVS Positive n=13 all true+ * SVS Indeterminate n=5 SVS Negative n=60 true-, 1 false- * Hu, Orthopaedic Research Society

19 Case 2 3T Siemens Verio NHP Pain Pt, 2-level PD+/- Discogram: +/- L1-L2 4mm L2-L3 5mm L3-L4 5mm 0 L4-L5 6mm 10 L5-S1 6mm 22

20 Results - Siemens 3T Verio Signal Quality Success 85% (100% Manual Shim, >1mm) 140 Technical Success, Signal Quality - Siemens 3T Verio % Lipid/motion Low SNR < 3x Poor Shim (WaterFWHM > 35Hz) Success 100 Discs (#) % % Both 1mm Voxels 40 80% 74 5% Discs 32 Subjects 95% 92 Discs 38 Discs 11 Subjects Total Autoshim only Auto+Manual Shim Protocol Development (Shim) 36 23

21 Results - Siemens 3T Verio Autoshim only vs. Auto+Manual Shim Example Asymptomatic Control Volunteer Autoshim Only (Fail Water FWHM) Auto+Manual shim L1L2 4mm L2L3 4mm N313 24

22 Conclusions disc SVS signal quality - reliability 100% robust disc spectra per signal quality 3mm disc height per later protocol refinements (autoshim + manual shim) of the Siemens 3T platform study 80% reliability w/ autoshim only 25

23 Results Siemens 3T Verio PG/LA Dx Correlation vs. Disc Type Controls (n=110) Disc SVS PG/LA Ratio vs. Disc Type log PG/LA Ratio, Lumbar Disc SVS n=1 n=1 n=8 n=100 0 PD+ 1 PD+ 2 PD+ 3 NC 4 5 Non-herniated Non-herniated,Spondy Herniated (PD- and ASY) 26

24 Combined Siemens & GE 3T Results PG & LA correlate 174/175 (>99%) discs, 72 subjects 100% 90% 80% Dx Correlation Results, GE & Siemens 3T Combined (PG & LA-based Dx Algorithms separately developed, MR platform-specific) 7% n=1 0% n=0 70% Discs (#) 60% 50% 40% 93% 100% n=13 n=161 30% 20% 10% Mis-Match vs. Control Match vs. Control 0% Painful Control Disc Type Non-Painful 27

25 Conclusions Combined PG & LA-related results from the two serial GE & Siemens 3T platform disc SVS development studies reflects >99% correlation between classic contained discogenic pain and non-painful discs in 175 total discs in 72 subjects 100% PPV for pain in 13 painful PD+ discs 0% False+ in 161 non-painful discs 28

26 Conclusions Disc SVS may be most appropriate for classic contained axial discogenic low back pain w/o extradiscal pain generators, vs. pain caused by extradiscal morbidities (e.g. herniations, facet, vertebral abnormalities) may still enhance Dx regimen in multi-factorial cases involving both intra-discal and extra-discal pain sources 29

27 Single Voxel MR Spectroscopy in Non-Herniated Painful, Herniated Painful, and Non-Painful Lumbar Discs PG Lactate col L Tanenbaum 1, S Hu 2, M Gornet 3, S Berven 2, J Peacock 4, J Lotz 2,4, D Bradford 4, J Claude 4, P Kane 4, F Schranck 3, D Stewart 5 1 Icahn School of Medicine at Mount Sinai, 2 University of California San Francisco, 3 Orthopedic Center of Saint Louis, 4 Nocimed, LLC, 5 MRI Partners of Chesterfield 30